Regulation of ZEB1 Function and Molecular Associations in Tumor Progression and Metastasis

Abstract

Zinc finger E-box binding homeobox 1 (ZEB1) is a pleiotropic transcription factor frequently expressed in carcinomas. ZEB1 orchestrates the transcription of genes in the control of several key developmental processes and tumor metastasis via the epithelial-to-mesenchymal transition (EMT). The biological function of ZEB1 is regulated through pathways that influence its transcription and post-transcriptional mechanisms. Diverse signaling pathways converge to induce ZEB1 activity; however, only a few studies have focused on the molecular associations or functional changes of ZEB1 by post-translational modifications (PTMs). Due to the robust effect of ZEB1 as a transcription repressor of epithelial genes during EMT, the contribution of PTMs in the regulation of ZEB1-targeted gene expression is an active area of investigation. Herein, we review the pivotal roles that phosphorylation, acetylation, ubiquitination, sumoylation, and other modifications have in regulating the molecular associations and behavior of ZEB1. We also outline several questions regarding the PTM-mediated regulation of ZEB1 that remain unanswered. The areas of research covered in this review are contributing to new treatment strategies for cancer by improving our mechanistic understanding of ZEB1-mediated EMT.